ABSTRACT Individuals with anorexia nervosa (AN) and bulimia nervosa (BN) have aberrant feeding behavior, and disturbances of emotionality and impulse control. Imaging studies from our last funding period suggest that these symptoms are related to dysfunction of limbic and cognitive circuits. This application will use blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) to examine neural substrates underlying appetitive, reward, and cognitive dysregulation in AN and BN. Over 5 years we will study 50 women recovered (REC) from AN and 50 female REC BN (to avoid the confounding effects of malnutrition and because considerable data suggests these symptoms are traits that persist after recovery) compared to 50 healthy control women (CW), all of whom are 18 to 45 years old. AIM 1: The anterior insula (AI) and related regions integrate sensory/hedonic aspects of taste and interoceptive awareness in the service of homeostasis. We will use a sucrose gustatory challenge and will provoke homeostasis by comparing a hungry state to a satiated state. Our data suggest that restricted eating and weight loss occurs in AN because feeding elicits diminished insula homeostatic response to hunger, whereas overeating in BN is related to exaggerated hunger signal. AIM 2: Several lines of evidence suggest that disturbed striatal function in AN contributes to anhedonia and over concern with future consequences. Using a delayed discounting task, we expect that REC AN will show a preference for later rewards compared to CW, reflecting aberrant anterior ventral striatum-limbic function, as well as overactive cognitive pathways, related to planning and assessment of consequences. AIM 3: Those with anorexia are rigid, inflexible, and behaviorally inhibited whereas BN have these traits as well as impulsivity and affective instability. We will use a validated motor inhibition task to characterize the neural substrates of inhibitory control. Preliminary data suggests REC AN show demand-specific alterations within a fronto-subthalamic circuit that is critically involved in motor inhibition and cognitive control. Taken together, these aims will enable us to better characterize cognitive and limbic dysfunction in these populations. Understanding biologic vulnerabilities in AN and BN is critical for developing effective treatment interventions for these often chronic and deadly disorders. This if the first resubmission of competing renewal MH042984